Valproate & Contraception

Contraception for individuals using valproate medicines

Pregnancy MUST be avoided during use of valproate medicines, which are highly teratogenic. Use of effective contraception is a requirement for prescription of valproate for any individual who has the potential to conceive.

Ideally, highly effective long-acting reversible contraception (LARC) should be used in this situation. This is because short-acting contraception relies on perfect use to be effective – with typical use such methods have a high contraceptive failure rate.

Valproate medicines include sodium valproate, valproic acid, valproate semisodium, Epilim, Convulex, Episenta, Epival, Epilim Chrono/Chronosphere, Dyzantil, Depakote, Syonel, Belvo.

Background information regarding valproate and the pregnancy prevention programme

Pregnancy must be avoided during use of valproate medicines. Valproate (a drug used for epilepsy and bipolar disorder) is a teratogen. If valproate medicines are used during pregnancy, there is a high risk that the baby will be affected by birth defect (which may be severe and permanent) and developmental abnormality (which could affect speech, language, intelligence and memory), as well as increased risk of autism and Attention Deficit Hyperactivity Disorder. Amongst children exposed to valproate in utero, 11% have congenital malformation and 30-40% have a neurodevelopmental disorder. It is extremely important, therefore, that pregnancy is avoided during use of valproate.

The UK Valproate Pregnancy Prevention Programme (‘Prevent’) aims to minimise exposure of pregnancies to valproate. Prevent mandates that:-

1. Valproate can be prescribed for individuals who have the potential to conceive a pregnancy only if two specialists consider that valproate is their only effective treatment option. For women of childbearing age on Valproate there is a requirement for an annual review and completion of the Annual Risk Assessment Form, outlined in the CMO’s letter on Valproate regulatory measures.

AND

•  Individuals with potential to conceive must use effective contraception continuously throughout valproate use.

MHRA guidance and supporting materials are available and there is also advice on the East Region Formulary.

Exclusion criteria for use of effective contraception during use of valproate medicines include:-

• Hysterectomy
• Bilateral oophorectomy
• Aged >50 years and confirmed post-menopause (i.e. at least 12 months of natural amenorrhoea after age 50 or 12 months after a serum FSH >30 that was taken after age 50)
• No sexual partners who were assigned male at birth.

Consideration of any other potential exclusion criteria should be made by the specialist overseeing prescription of the valproate medicine.

Contraceptive options during use of valproate medicines

Highly effective contraceptive methods should be recommended during use of valproate. These are methods that do not rely on the user to ensure correct use and are >99% effective for contraception. They include:-

• Copper intrauterine devices (Cu-IUD)
• Levonorgestrel-releasing intrauterine devices (LNG-IUD – available as LNG 52mg, 19.5mg and 13.5mg devices)
• Etonogestrel subdermal implants (ENG-IMP, Nexplanon^®)*
• Female sterilisation
• Male sterilisation

(Note that there is a wait for both female and male sterilisation procedures and that after male sterilisation the contraception should not be relied upon until follow up semen analysis is complete. Interim effective contraception is required).

If a combined hormonal contraceptive (CHC), progestogen-only pill (POP) or progestogen-only contraceptive injection (POI) is used, additional use of condoms should be recommended. Combined hormonal contraception (the combined hormonal pill, transdermal patch and vaginal ring), progestogen-only contraceptive pills and depot medroxyprogesterone acetate injections offer effective contraception if used absolutely perfectly*. These methods are, however, highly user-dependent, and with typical use, the risk of pregnancy during the first year of use is estimated at 6-9%. Additional consistent, correct use of condoms should be advised in addition to these methods.

*Note that valproate is not an enzyme-inducing drug. If, however, an individual using valproate is also using a drug that is an enzyme inducer this would reduce contraceptive effectiveness of the ENG-IMP, CHC and POP. In this instance, highly effective methods of contraception that are not affected by enzyme inducers (Cu- IUD, LNG-IUD, sterilisation) would be recommended. If these methods are not suitable/acceptable, depot medroxyprogesterone acetate injections could be considered (their effectiveness is not affected by enzyme induction) but additional use of condoms should be recommended because the typical use failure rate of POI is much higher than LARC methods and sterilisation. 

The typical use contraceptive failure rate of condoms, internal condoms and contraceptive diaphragms and caps, fertility awareness methods and apps is high. These methods should not be relied upon to prevent pregnancy during use of valproate, and alternative, effective contraception should be offered.

If an individual who is using valproate requires emergency contraception

• a Cu-IUD should be offered first line if criteria for use are met as it is much more effective than oral emergency contraception
• if a Cu-IUD is accepted, but cannot be immediately inserted, offer oral emergency contraception IN ADDITION (if appropriate) in case the Cu-IUD insertion is unsuccessful or the individual later declines the Cu-IUD
• if a Cu-IUD is not appropriate, or is not acceptable, oral emergency contraception should be offered if appropriate
• offer immediate start of effective ongoing contraception (delay for 5 days after ulipristal acetate oral emergency contraception – e.g. EllaOne®)
• see decision-making algorithms 1 and 2 for emergency contraception at Faculty of Sexual and Reproductive Healthcare Emergency Contraception Guideline

If an individual with potential to conceive is using valproate and wishes to discontinue their current effective contraception:-

• explain the importance of effective contraception during valproate use
• offer alternative effective contraception, and ensure immediate start of the new method
• if the individual declines effective alternative contraception, advise that discussion with the specialist overseeing their valproate use is required prior to stopping effective contraception, make an urgent referral to the Complex Contraception Clinic at Chalmers and inform their specialist and their GP of their wish to discontinue contraception.

The individual’s GP and the specialist overseeing their valproate prescription MUST be made aware of any changes to contraception.

C.M. & L.M, S.H 22-05-24